One of the most unique characteristics of the H-2 complex, the major histocompatibility complex of the mouse, is the polymorphism of its loci, that is the fact that a large number of alleles at each of the H-2 loci occur with appreciable frequencies in natural mouse populations. The objective of the proposed study is to determine the extent of the H-2 polymorphism, the mechanism of its maintenance, and the relation of the polymorphism to the function of the H-2 complex. The extent of the H-2 polymorphism will be ascertained using various assays of H-2 typing: serological typing with antibodies against classical H-2 and Ia antigens, mixed lymphocyte reaction, cell-mediated lymphocytotoxicity, and tests for the immune response to synthetic polypeptides. The starting point of these studies will be a set of congenic lines carrying, on an inbred background, H-2 haplotypes derived from wild mice. From these lines, the study will then be extended to natural mouse populations. The mechanism of the maintenance of the H-2 polymorphism will be explored by determining how this polymorphism is affected by the t complex and by the mouse population structure. It is expected that the elucidation of the population behavior of the individual H-2 loci and of the interrelationships of these loci will provide a clue to the understanding of the H-2 function.